Effect of the anti-diabetic drug metformin in hepatocellular carcinoma in vitro and in vivo
Autor: | Shima Mimura, Emiko Maeda, Takashi Himoto, Teppei Sakamoto, Yasuyuki Suzuki, Hideki Kobara, Yuka Toyota, Hisaaki Miyoshi, Kiyohito Kato, Takako Nomura, Keiichi Okano, Koji Fujita, Tsutomu Masaki, Asahiro Morishita, Hisakazu Iwama, Kazutaka Kurokohchi, Hirohito Yoneyama, Akihiro Deguchi, Mitsuyoshi Kobayashi, Joji Tani, Hirohito Mori, Koji Murao |
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Rok vydání: | 2014 |
Předmět: |
Cancer Research
medicine.medical_specialty Carcinoma Hepatocellular Cyclin E endocrine system diseases medicine.drug_class Mice Nude Antineoplastic Agents Biology Mice Liver Neoplasms Experimental Cyclin D1 In vivo Cell Line Tumor Internal medicine medicine Animals Humans Oncogene Biguanide Cell growth Cell Cycle Liver Neoplasms digestive oral and skin physiology nutritional and metabolic diseases Cell cycle Xenograft Model Antitumor Assays Metformin Gene Expression Regulation Neoplastic MicroRNAs Endocrinology Oncology Cancer research medicine.drug |
Zdroj: | International Journal of Oncology. 45:322-332 |
ISSN: | 1791-2423 1019-6439 |
Popis: | Metformin is a commonly used oral anti-hyperglycemic agent of the biguanide family. Recent studies suggest that metformin may reduce cancer risk and improve prognosis. However, the antitumor mechanism of metformin in several types of cancers, including hepatocellular carcinoma (HCC), has not been elucidated. The goal of the present study was to evaluate the effects of metformin on HCC cell proliferation in vitro and in vivo, and to study microRNAs (miRNAs) associated with the antitumor effect of metformin in vitro. We used the cell lines Alex, HLE and Huh7, and normal hepatocytes to study the effects of metformin on human HCC cells. In an in vivo study, athymic nude mice bearing xenograft tumors were treated with metformin or left untreated. Tumor growth was recorded after 4 weeks, and the expression of cell cycle-related proteins was determined. Metformin inhibited the proliferation of Alex, HLE and Huh7 cells in vitro and in vivo. Metformin blocked the cell cycle in G0/G1 in vitro and in vivo. This blockade was accompanied by a strong decrease of G1 cyclins, especially cyclin D1, cyclin E and cyclin-dependent kinase 4 (Cdk4). In addition, microRNA (miRNA) expression was markedly altered by the treatment with metformin in vitro and in vivo. In addition, various miRNAs induced by metformin also may contribute to the suppression of tumor growth. Our results demonstrate that metformin inhibits the growth of HCC, possibly by inducing G1 cell cycle arrest through the alteration of microRNAs. |
Databáze: | OpenAIRE |
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